If mass spectrometry has to measure the masses of large molecules, particularly those occurring in biochemistry, time-of-flight mass spectrometers are more suitable than other types of spectrometers because of the restricted mass ranges of other mass spectrometers. Time-of-flight mass spectrometers are often referred to by the abbreviation TOF or TOF-MS.
Two different types of time-of-flight mass spectrometer have developed. The first type comprises time-of-flight mass spectrometers for the measurement of ions generated in extremely short pulses in very small volumes of origin, for example by matrix assisted laser desorption (abbreviated to MALDI), a method of ionization appropriate for the ionization of large molecules.
The second type comprises time-of-flight mass spectrometers for the continuous injection of a primary beam of ions, a segment of which is then ejected in a “pulser” transverse to the primary beam direction into the time-of-flight mass spectrometer as a linearly extended bundle of ions. This generates a ribbon-shaped ion beam. This second type is referred to for short as an orthogonal time-of-flight mass spectrometer (OTOF); it is mainly applied in association with out-of-vacuum ionization by electrospray (ESI). The application of a very large number of pulses in a given time (up to 50,000 pulses per second) produces a large number of spectra, each based on a small number of ions, in order to exploit the ions in the continuous primary ion beam most effectively. Similar to MALDI, ESI is also suitable for the ionization of large molecules.
FIG. 1 shows a schematic diagram of a time-of-flight mass spectrometer with orthogonal ion injection according to prior art. A beam of ions of different initial energies and initial angles passes through an aperture (1) in an ion-guide system (4) and enters the ion-guide system (4) which is housed in a gas-tight casing. A damping gas is introduced into the ion-guide system along with the ion beam. The ions entering the chamber are decelerated by collision in the gas. Since there is a pseudo-potential for the ions in the ion-guide system which is at its lowest at the axis (5), the ions collect at the axis (5). The ions spread at the axis (5) to the end of the ion-guide system (4). The gas is pumped from the ion-guide system to the vacuum chamber (2) by the vacuum pump (6).
At the end of the ion guide system (4) there is a lens system (7), the second apertured diaphragm of which is integrated in the wall (8) between the vacuum chamber (2) for the ion-guide system (4) and the vacuum chamber (9) for the time-off-light mass spectrometer. In this case, the drawing lens system (7) consists of five apertured diaphragms. It draws the ions from the ion-guide system (4) to produce a fine primary ion beam with a small phase space volume which is focused into the pulser (12). The ion beam is injected into the pulser in the x direction. When the pulser is full of the ions of the preferred masses to be analyzed, in transit, a short voltage pulse propels a wide segment of the ion beam transverse to the previous flight direction in the y direction and forms a wide ion beam which is reflected in a reflector (13) and measured by an ion detector (14) with a high time resolution. In the ion detector (14), the ion signal, which is amplified by a secondary electron amplifier in the form of a double, multi-channel plate, is transmitted capacitively to a 50Ω cone. This signal, which has thus already been amplified, is passed to an amplifier via a 50Ω cable. The cable on the input end is terminated by the 50Ω cone so that no signal reflection can take place at this point.
In this prior art, the reflector (13) and detector (14) are oriented exactly parallel to the x direction of the ions injected into the pulser. The distance between the detector (14) and the pulser (12) determines the maximum level of utilization of ions from the fine ion beam.
In principle, the pulser has a very simple construction; the pulser region into which the parallel primary ion stream is injected in the x-direction is located between a pusher (or repeller) diaphragm and a puller diaphragm. The pusher does usually not have any apertures. The puller either has a grid or a fine slit through which the ions are ejected by pulsed acceleration in the y-direction.
The pusher and puller here only carry a small proportion of the entire acceleration voltage. One reason for this is that high voltages cannot be switched at high enough speeds. However, the main reason is that it is possible to time-focus ions of a single mass which are at different distances from the detector in the cross section of the fine primary ion beam when outpulsed (start location focusing according to Wiley and McLaren) because the field strength is adjustable. A compensation diaphragm is positioned after the puller and this suppresses penetration of the main acceleration field into the pulser region. Between the puller and the field-free drift region of the mass spectrometer, at least one additional diaphragm generates the main acceleration field, which provides the major proportion of the acceleration of the ions up to the drift region. The potential is held static on the diaphragms for the main acceleration field. The drift region usually has no field.
In the pulser, the ions are accelerated perpendicular to their x direction and leave the pulser through the slits in the slit diaphragms. The direction of acceleration is referred to as the y direction. However, after acceleration, the ions travel in a direction which lies between the y direction and the x direction since they retain their original velocity in the x direction undisturbedly. The angle to the y direction is α=arctan √(Ex/Ey), where Ex is the kinetic energy of the ions in the primary beam in the x direction and Ey is the energy of the ions after acceleration in the y direction.
In commercially manufactured devices, the interior of the pulser has always been separated from the static electrical field of the main acceleration region by a grid. This means that the ions are pulsed out through the grid. Penetration of the main acceleration field through the grid during the filling phase is relatively slight, and can be controlled. In the literature, however, pulsers with slit diaphragms are also described.
The ions leaving the pulser now form a broad ribbon where ions of the same type and mass are located in a front in each case, the front being as wide as the ejected beam segment in the pulser. Light ions travel faster and heavy ions travel slower, but all travel predominantly in the same direction apart from small differences in direction arising from the slightly different kinetic energies Ex of the ions when injected into the pulser. The field-free flight path must be completely surrounded by the acceleration potential so that the flight of the ions is not subject to interference.
According to Wiley and McLaren, ions of the same mass which are at different places in the cross section of the beam and therefore have different distances to travel to reach the detector can be time-focused in relation to their different start locations. This can be achieved by the following method: when the outpulse voltage is switched on, the field in the pulser is selected in such a way that the ions furthest away acquire a somewhat higher acceleration energy. This enables them to catch up again with the ions which were ahead at a “start location focal point”. The position of the start location focal point can be chosen at will by adjusting the outpulse field strength in the pulser.
In order to achieve high resolution, the mass spectrometer is fitted with an energy-focusing reflector. This reflects the outpulsed ion beam in its entire width toward the ion detector, and provides an accurate time focus at the wide-surface detector for ions of the same mass but with slightly different initial kinetic energies in the y direction.
In prior technology, the reflector is always set up so that the plane of entry runs parallel to the x direction, i.e., parallel to the original direction of the fine ion beam injected into the pulser, as shown in FIG. 1. Ions of the same mass, which form a front in the newly formed ion beam, then enter the reflector at the same time, stop at the same time and are accelerated back in the same way and leave the reflector again at the same time. In the homogeneous reflection field, the ion paths have the form of flight parabolas. (In FIG. 1, the parabolas are approximated by triangles).
The ions travel from the reflector to a detector, which must be as wide as the ion beam in order for all the ions arriving to be measured. The detector must also be aligned exactly parallel to the x direction, as shown in FIG. 1, in order for all the ions of the same mass to be detected simultaneously.
A continuous stream of ions in the form of a fine primary ion beam is injected into the pulser in the x direction. The pulser begins to fill immediately after the ions of the last outpulsing cycle have left the pulser. After perpendicular ejection, the velocity of the ions in the x direction remains unaltered, in spite of the deflection perpendicular to the x direction. After lateral acceleration in the y direction and reflection in the reflector, the ions reach the detector in the same time they would have needed to reach this detector location by a straight, undeflected path (although they would then miss the detector since they would be flying parallel to the detector surface).
When the ions of highest mass have arrived at the detector, then not only is the pulser again filled with the heaviest ions but also the region between the pulser and the frontal side of the detector. However, it is only possible to analyze, in the next cycle, those ions which are in the detector at the time of the next outpulse. The ions in the region between the pulser and the detector are lost to the analysis. It is therefore apparent that the detector must be located as near to the pulser as possible for a high level of utilization of the ion beam. For a hundred percent utilization of the heavy ions, the pulser and the detector must touch each other (which is impossible for various physical reasons).
Considered more precisely, this applies only to the heaviest ions which are to be measured using this device. Only the heaviest ions determine the pulse rate to be used for the pulser as soon as it is full of the heaviest ions. A fraction of the lighter ions, which travel faster, have already left the pulser. Ions which only weigh a tenth of the heaviest ions travel faster by a factor of √10≈3.16. Only a third of them, at most, therefore remain in the pulser and only this third is outpulsed in the y direction.
However, problems arise from having a short distance between the pulser and the detector. On the one hand, the detector is a highly sensitive measuring device which responds to the switching in the pulser due to capacitative crosstalk which gives rise to spurious interference signals. The detector must be well screened from the pulser, and good screening requires space. On the other hand, the pulser needs to be longer than the ejected segment of ejected ions. Furthermore, in order to adjust the mass spectrometer, it is desirable to be able to measure the fine stream of ions—which is injected into the pulser when it is switched off hand travels through it to appear again at the other end—very precisely in a second detector. The second detector requires space. This measurement is therefore not possible if a short distance is required between the pulser and the detector.
If necessary, it is possible to place the pulser and the detector in different) planes. Because of the way it is designed with its 50Ω cone, the detector cannot be pushed nearer to the reflector since its cone will still end up lying next to the pulser. A position further away from the reflector involves making the mass spectrometer larger again, which is also undesirable.